The human nervous systems, both central and peripheral, are dynamic entities. One way this dynamic nature of both nervous systems is expressed is a constant change in the way neurons are connected or arranged to allow communication therebetween. Communication in the nervous system includes signalling or information transfer within and between the neurons. The structure of a neuron is unique and reflects this essential function of the nervous system. In addition to the neuron cell body, called the soma, which is structurally similar to other biological cells, the neuron also features two characteristic structural elements that are essential for the signalling process, namely the axon and the dendrite.
The axon is a cell structure specialised for intracellular transfer of information over long distances. An axon originates at a cone-shaped thickening on the cell body called the axon hillock. Information is transmitted within neurons via electrical signals. Such electrical signals are represented by the action potential, which is a single, transient reversal of membrane polarity. The action potential is the basic unit of signalling in the neural system. The intracellular information transfer is carried out by conduction of the action potential along the axon and this conducting mechanism is known as saltatory conduction.
The synaptic terminal is situated at the opposite end of the axon. The synaptic terminal contains synaptic vesicles, which play an important role in interneural communication.
Many, but not all, axons in a vertebrate nervous system are surrounded by a myelin sheath. This sheath is formed by oligodendrocytes on central nervous system axons and by Schwann cells in the peripheral nervous system. The sheath is not a continuous structure but features gaps several microns wide. These gaps are known as the nodes of Ranvier and play an important role in intraneural transport of information.
The dendrite is a cell structure specialised to receive information from other neurons. Dendrites, in general, are shorter than axons, frequently highly branched, and form a dense network known as a dendritic tree.
Another important structural entity necessary for signalling is the synapse. The synapse is a highly specialised structure that mediates the transfer of information from one neuron to another. In general, the term synapse refers to the junction where communication occurs between two excitable cells, e.g. neuron and neuron, or neuron and muscle cell. Synapses and synaptic transmission can be electrical and chemical, depending on the nature of the information transfer.
In a typical chemical synapse, a branch of the afferent or presynaptic axon swells at its terminus to form a bouton, which is very close to, but does not actually physically touch the specialised postsynaptic side of the synapse. Most neurons have a dendrite that is capable of responding to a chemical signal transmitted from the presynaptic axon. The gap between the two communicating neurons is typically 20 nm wide and is called the synaptic cleft. The fluid-filled gap between the two neurons prevents the direct transfer of electrical current from one neuron to another. The signal transfer between the neurons is instead carried out by rapid diffusion of naturally occurring chemicals called neurotransmitters. The molecules comprising the neurotransmitters in a presynaptic neuron are contained within synaptic vesicles. The signal transmission occurs by synaptic vesicles fusing with the cell membrane of the presynaptic neuron, excreting the neurotransmitters molecules to the cleft which than rapidly diffuse and interact with the postsynaptic neuron where it may produce either an excitatory or inhibitory postsynaptic potential.
Frequently, the number of neurons that sense information about an environment is measured in the thousands and this information, collected by a large number of sensors, is imported into the brain for processing. Whilst information between two neurons is still transmitted through the synapse, a network of interacting cells is required for the full spectrum of information to be collected and transferred to the brain.
Signalling is essential for an organism if it wishes to:
1. Sense information about an environment;
2. Import that information into its brain where it can be processed; and
3. Generate a behavioural response.
Neural rearrangements are a necessary part of a normal developmental process. However, neural rearrangements may also occur as an organism's response to events that inhibit natural functionality. For example, functional and structural changes in the auditory system of a person may effect the way that person perceives sound and may even deprive them from receiving sound at all. Frequently though, even though there are substantial changes in functionality of the auditory system, such as sensorineural loss of hearing, organisation of the auditory system is maintained.
The auditory system can be divided into two large subsystems, namely the peripheral auditory system and the central auditory system.
The peripheral auditory system converts the condensation and rarefaction of air that produces sound into neural codes that are interpreted by the central auditory system as specific sound tokens.
The peripheral auditory system is subdivided into the external ear, the middle ear, and the inner ear. The external ear collects the sound energy as pressure waves which are converted to mechanical motion of the eardrum. This motion is transformed across the middle ear and transferred to the inner ear, where it is frequency analysed and converted into neural codes that are carried by the eighth cranial nerve, ie. the auditory nerve, to the central auditory system.
Sound information, encoded as discharges in an array of thousands of auditory nerve fibers, is processed in nuclei that make up the central auditory system. The major centers include the cochlear nuclei (CN), the superior olivary complex (SOC), the nuclei of the lateral leminiscus (NLL), the inferior colliculi (IC), the medial geniculate body (MGB) of the thalamus, and the auditory cortex (AC). The CN, SOC, and NLL are brainstem nuclei, while the IC is at the midbrain level and the MGB and AC constitute the auditory thalamocortical system.
Sound, in a form of a mechanical wave, enters the cochlea at the round window. The cochlea is filled with fluid and the mechanical wave travels firstly through the scala vestibuli upwardly towards the apical part of the cochlea. At the very top of the cochlea, the scala vestibule and scala tympani connect through the helicotrema. As the mechanical wave travels downwardly through the scala tympani it initiates displacement in the basilar membrane. This motion has frequency-dependent characteristics which arise from properties of the membrane and surrounding structures.
Displacement of the basilar membrane is sensed by the inner hair cells, through a mechanism involving the Organ of Corti, and at this point the mechanical signal is encoded to an electrical signal. Such an electrical signal is then transferred through radial fibers to the spiral ganglion cells.
The electrical signal is further transmitted to the cochlear nucleus, which is the first obligatory synapse in the ascending auditory path, and then further as described previously. The frequency-dependant characteristics of the basilar membrane are reflected in the fact that the membrane is more responsive to low frequency sound at the apical end of the cochlea, and to high frequency sound at the basal end of the cochlea. In general, such frequency or tonotopic organisation of the basilar membrane is transferred to the hair cells and to the rest of the auditory system. The auditory system is organised tonotopically, ie. in order of frequency, because the frequency ordering of the cochlea is mapped through successive levels of the system.
This tonotopic organisation of the auditory system can be represented by threshold curves which are also called tuning curves. The threshold tuning curves for axons in the auditory nerve show a minimal threshold (maximum sensitivity) at a characteristic frequency with a narrow frequency range of responding for slightly more intense sounds. A threshold level can be identified as a minimum intensity that would evoke a discharge rate significantly higher than the spontaneous discharge rate. The threshold or neural tuning curve is not to be confused with the mechanical tuning curve which shows how the stimulus intensity must be changed relative to frequency so that a particular point on the basilar membrane always has the same deflection amplitude. The width of the tuning curves can be used as a measure of selectivity, or ability to discriminate between sounds.
Further, the auditory system is designed to accept signals from two independent sources, ie. two ears. The normal existence of two independent inputs has an important role in a number of processes such as sound localisation.
An apparatus for delivering random patterns of activation to the auditory nerve to generate psuedospontaneous activity in the nerve is described in U.S. Pat. No. 6,295,472. While this system is described as useful for treating tinnitus, the patent does not describe use of an apparatus that delivers stimulation in a manner that controls the production and/or release of naturally occurring agents into the auditory system.
In recent times, a high degree of hearing loss in both ears (profound loss of hearing) has been successfully treated with a cochlear implant.
Successful use of a cochlear implant rests with the fact that the spiral ganglion cells (SGC) and the rest of the auditory system through to the auditory cortex are still fully functional in the implantee. It is important to note that the cochlear implant does not restore the function of damaged (ie. non-functional) parts of the auditory system, primarily the inner hair cells, but actually presents spiral ganglion neurons with electrical activity that in normal hearing subjects is generated by the hair cells and transferred by the radial fibres to the spiral ganglion cells.
The cochlear implant analyses sound and encodes it in a train of electrical pulses that stimulate the auditory nerve fibres. The train of pulses carry both frequency and time information. All currently available cochlear implants achieve this task through stimulation of nerve fibres by activation of multiple stimulating electrodes located on a flexible carrier inserted in the cochlea. Successful use of a cochlear implant is associated with a habituation process during which a cochlear implant user learns to interpret electrical signals presented by the implant as meaningful sound.
As a result of the presented electrical stimulation to the SGC, major changes in the auditory system of the implantee may occur. The cochlear implant is generally implanted in only one ear, resulting in stimulus coming from one source instead of two source. Secondly, even the presently most advanced cochlear implants only have a very limited number of stimulating pads, typically between 6 and 22 electrodes. This is in contrast to normal hearing people where the received auditory stimulus is processed by between 3000-4000 hair cells.
As a result of facilitated activity of the SGC in one cochlea only and stimulation through a very limited number of stimulating electrodes, the neural paths that transport signal from the SGC to the auditory cortex may undergo rearrangements with certain synapses disappearing and other completely new synapses being formed to reflect the patterns of neural activity. Such rearrangement of the neural path is essentially uncontrolled and normal use of a cochlear implant does not provide any mechanism for the controlled modification of the neural paths of the implantee.
The efficiency and potential benefits that the cochlear implant may provide heavily depend on the plasticity of the neural system of the implantee. For example, it is well known that efficiency of the implant decreases as the length of deafness, particularly in prelingually deaf people, increases.
Some other examples where neural rearrangements occur as a consequence of an injury or treatment of the injury include, but are not limited to, visual impairment, sensorineural and motorneural injuries. Further, the device may be used to treat abnormal functionality of part of a neural system. Sensorineural and motorneural abnormalities, such as depression, Parkinson's disease, Alzheimer's disease may also be treated with the herein described device. These diseases may be treated at present with naturally occurring agents, administered to a patient through a mechanism(s) other than electrical stimulation, e.g. oral administration of agents in a form of a tablet.
The present invention is in part directed to an apparatus that is adapted to improve or maintain the plasticity of the neural system of a patient with a cochlear implant.
Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application.